Long non-coding RNAs (lncRNAs) comprise a diverse class of RNA transcripts >200 nucleotides in length with limited protein-coding potential. In addition to their possible role in cancer biology, ...circulating lncRNAs have emerged as a new class of promising cancer biomarkers, with independent studies demonstrating the feasibility of their use as tools in the diagnosis and prognosis of different types of malignancies and for predicting and possibly monitoring treatment response. However, critical issues are represented by nonuniform sample choice, handling and processing, blood cell contamination during sample preparation and the lack of consensus regarding data normalization. In this review, we discuss the value of circulating lncRNAs in the clinical setting, particularly with respect to their possible implementation as diagnostic and prognostic markers in cancer. Although the great potential of circulating lncRNAs as cancer biomarkers would be an important development in disease management, both intrinsic and extrinsic factors that may affect their measurement have not been fully characterized. Moreover, the clinical significance of circulating lncRNA may not be proven without a global consensus regarding procedures and standardized protocols for their detection.
Intravenous arsenic trioxide plus all-trans retinoic acid (ATRA) without chemotherapy is the standard of care for non-high-risk acute promyelocytic leukaemia (white blood cell count ≤10 × 109 per L), ...resulting in cure in more than 95% of cases. However, a pilot study of treatment with oral arsenic realgar-Indigo naturalis formula (RIF) plus ATRA without chemotherapy, which has a more convenient route of administration than the standard intravenous regimen, showed high efficacy. In this study, we compare an oral RIF plus ATRA treatment regimen with the standard intravenous arsenic trioxide plus ATRA treatment regimen in patients with non-high-risk acute promyelocytic leukaemia.
We did a multicentre, non-inferiority, open-label, randomised, controlled phase 3 trial at 14 centres in China. Patients aged 18–70 years with newly diagnosed (within 7 days) non-high-risk acute promyelocytic leukaemia, and a WHO performance status of 2 or less were eligible. Patients were randomly assigned (2:1) to receive treatment with RIF-ATRA or arsenic trioxide-ATRA as the induction and consolidation therapy. Randomisation was done centrally with permuted blocks and stratification according to trial centre and was implemented through an interactive web response system. RIF (60 mg/kg bodyweight daily in an oral divided dose) or arsenic trioxide (0·15 mg/kg daily in an intravenous dose) and ATRA (25 mg/m2 daily in an oral divided dose) were used until complete remission was achieved. The home-based consolidation therapy was RIF (60 mg/kg daily in an oral divided dose) or intravenous arsenic trioxide (0·15 mg/kg daily in an intravenous dose) in a 4-week on 4-week off regimen for four cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week on 2-week off regimen for seven cycles. Patients and treating physicians were not masked to treatment allocation. The primary outcome was event-free survival at 2 years. A non-inferiority margin of −10% was used to assess non-inferiority. Primary analyses were done in a modified intention-to-treat population of all patients who received at least one dose of their assigned treatment and the per-protocol population. This study was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-13004054), and the trial is complete.
Between Feb 13, 2014, and Aug 31, 2015, 109 patients were enrolled and assigned to RIF-ATRA (n=72) or arsenic trioxide-ATRA (n=37). Three patients in the RIF-ATRA and one in the arsenic trioxide-ATRA did not receive their assigned treatment. After a median follow-up of 32 months (IQR 27–36), 67 (97%) of 69 patients in the RIF-ATRA group and 34 (94%) of 36 in the arsenic trioxide-ATRA group had achieved 2-year event-free survival in the modified intention-to-treat population. The percentage difference in event-free survival was 2·7% (95% CI, −5·8 to 11·1). The lower limit of the 95% CI for the difference in event-free survival was greater than the −10% non-inferiority margin, confirming non-inferiority (p=0·0017). Non-inferiority was also confirmed in the per-protocol population. During induction therapy, grade 3–4 hepatic toxic effects (ie, increased liver aspartate aminotransferase or alanine transaminase concentrations) were reported in six (9%) of 69 patients in the RIF-ATRA group versus five (14%) of 36 patients in the arsenic trioxide-ATRA group; grade 3–4 infection was reported in 15 (23%) of 64 versus 15 (42%) of 36 patients. Two patients in the arsenic trioxide-ATRA group died during induction therapy (one from haemorrhage and one from thrombocytopenia).
Oral RIF plus ATRA is not inferior to intravenous arsenic trioxide plus ATRA for the treatment of patients with non-high-risk acute promyelocytic leukaemia. This study suggests that a completely oral, chemotherapy-free model might be an alternative to the standard intravenous treatment for patients with non-high-risk acute promyelocytic leukaemia.
Foundation for innovative research group of the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the National Key R&D Program of China, and the National Natural Science Foundation of China.
Autism spectrum disorder (ASD) is a multifaceted neuropsychiatric condition for which effective drug therapy for core clinical symptoms remains elusive. Lotusine, known for its neuroprotective ...properties in the treatment of neurological disorders, holds potential in addressing ASD. Nevertheless, its specific efficacy in ASD remains uncertain. This study aims to investigate the therapeutic potential of lotusine in ASD and elucidate the underlying molecular mechanisms. We induced an ASD mouse model through intracerebroventricular‐propionic acid (ICV‐PPA) injection for 7 days, followed by lotusine administration for 5 days. The efficacy of lotusine was evaluated through a battery of behavioral tests, including the three‐chamber social test. The underlying mechanisms of lotusine action in ameliorating ASD‐like behavior were investigated in the medial prefrontal cortex (mPFC) using whole‐cell patch‐clamp recordings, western blotting, immunofluorescence staining, molecular docking, and cellular thermal shift assay. The efficacy and mechanisms of lotusine were further validated in vitro. Lotusine effectively alleviated social deficits induced by ICV‐PPA injection in mice by counteracting the reduction in miniature excitatory postsynaptic current frequency within the mPFC. Moreover, lotusine enhanced neuronal activity and ameliorated α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor dysfunction in ICV‐PPA infusion mice by upregulating c‐fos, p‐GluA1 Ser 845, and p‐GluA1 Ser 831 protein levels within the mPFC. Our findings also suggest that lotusine may exert its effects through modulation of the D1 dopamine receptor (DRD1). Furthermore, the rescuing effects of lotusine were nullified by a DRD1 antagonist in PC12 cells. In summary, our results revealed that lotusine ameliorates ASD‐like behavior through targeted modulation of DRD1, ultimately enhancing excitatory synaptic transmission. These findings highlight the potential of lotusine as a nutritional supplement in the treatment of ASD.
Lotusine ameliorates autism spectrum disorder‐like behaviorby activating D1 dopamine receptor.
Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a ...signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.
Due to the need to repeatedly call a classifier to evaluate individuals in the population, existing evolutionary feature selection algorithms have the disadvantage of high computational cost. In view ...of it, this paper studies a multi-objective feature selection framework based on sample reduction strategy and evolutionary algorithm, significantly reducing the computational cost of algorithm without affecting optimal results. In the framework, a selection strategy of representative samples, called K-means clustering based differential selection, and a ladder-like sample utilization strategy are proposed to reduce the size of samples used in the evolutionary process. Moreover, a fast multi-objective evolutionary feature selection algorithm, called FMABC-FS, is proposed by embedding an improved artificial bee colony algorithm based on the particle update model into the framework. By applying FMABC-FS to several typical UCI datasets, and comparing with three multi-objective feature selection algorithms, experimental results show that the proposed variable sample size strategy is more suitable to FMABC-FS, and FMABC-FS can obtain better feature subsets with much less running time than those comparison algorithms.
•Establishing a multi-objective evolutionary feature selection framework to reduce the computational cost of algorithm without affecting the result of feature selection.•Developing a K-means clustering based differential selection strategy and a ladder-like utilization strategy of samples to select representative samples for evaluating individuals.•Proposing a fast multi-objective feature selection algorithm, called FMABC-FS, by embedding an improved ABC algorithm into the framework.
Developing efficient organic solar cells (OSCs) with thick active layers is crucial for roll‐to‐roll printing. However, thicker layers often result in lower efficiency. This study tackles this ...challenge using a polymer adsorption strategy combined with a layer‐by‐layer approach. Incorporating insulator polystyrene (PS) into the PM6:L8‐BO system creates PM6+PS:L8‐BO blends, effectively suppressing trap states and extending exciton diffusion length in the mixed donor domain. Adding insulating polymers with benzene rings to the donor enhances π–π stacking of donors, boosting intermolecular interactions and electron wave function overlap. This results in more orderly molecular stacking, longer exciton lifetimes, and higher diffusion lengths. The promoted long‐range exciton diffusion leads to high power conversion efficiencies of 19.05% and 18.15% for PM6+PS:L8‐BO blend films with 100 and 300 nm thickness, respectively, as well as a respectable 16.00% for 500 nm. These insights guide material selection for better exciton diffusion, and offer a method for thick‐film OSC fabrication, promoting a prosperous future for practical OSC mass production.
This study addresses the challenge of maintaining efficiency in thick‐film organic solar cells (OSCs). A novel polymer adsorption strategy that regulates molecular stacking, leading to enhanced intermolecular interactions. A reduction in trap states and an elongation in exciton diffusion length, resulting in a remarkable increase in power conversion efficiency in thick‐film OSCs, is achieved.
It′s just a phase: The title reaction sequence of para‐quinone methides (p‐QMs) has been developed with malonates under phase‐transfer catalysis. The reaction also offers an alternative route to ...asymmetric construction of diarylmethine stereocenters in excellent enantioselectivities and high yields.
Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first ...genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.
Oxidative dispersion has been widely used in regeneration of sintered metal catalysts and fabrication of single atom catalysts, which is attributed to an oxidation-induced dispersion mechanism. ...However, the interplay of gas-metal-support interaction in the dispersion processes, especially the gas-metal interaction has not been well illustrated. Here, we show dynamic dispersion of silver nanostructures on silicon nitride surface under reducing/oxidizing conditions and during carbon monoxide oxidation reaction. Utilizing environmental scanning (transmission) electron microscopy and near-ambient pressure photoelectron spectroscopy/photoemission electron microscopy, we unravel a new adsorption-induced dispersion mechanism in such a typical oxidative dispersion process. The strong gas-metal interaction achieved by chemisorption of oxygen on nearly-metallic silver nanoclusters is the internal driving force for dispersion. In situ observations show that the dispersed nearly-metallic silver nanoclusters are oxidized upon cooling in oxygen atmosphere, which could mislead to the understanding of oxidation-induced dispersion. We further understand the oxidative dispersion mechanism from the view of dynamic equilibrium taking temperature and gas pressure into account, which should be applied to many other metals such as gold, copper, palladium, etc. and other reaction conditions.
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